scholarly journals Adaptive Balance in Posterior Cerebellum

2021 ◽  
Vol 12 ◽  
Author(s):  
Neal H. Barmack ◽  
Vito Enrico Pettorossi
Keyword(s):  
Purkinje Cells ◽  
Stellate Cell ◽  
Semicircular Canals ◽  
Mossy Fibers ◽  
Vestibular Nuclei ◽  
Three Dimensions ◽  
Optokinetic Stimulation ◽  
Afferent Pathways ◽  
Vestibular Nuclear Neurons ◽  
Self Motion

Vestibular and optokinetic space is represented in three-dimensions in vermal lobules IX-X (uvula, nodulus) and hemisphere lobule X (flocculus) of the cerebellum. Vermal lobules IX-X encodes gravity and head movement using the utricular otolith and the two vertical semicircular canals. Hemispheric lobule X encodes self-motion using optokinetic feedback about the three axes of the semicircular canals. Vestibular and visual adaptation of this circuitry is needed to maintain balance during perturbations of self-induced motion. Vestibular and optokinetic (self-motion detection) stimulation is encoded by cerebellar climbing and mossy fibers. These two afferent pathways excite the discharge of Purkinje cells directly. Climbing fibers preferentially decrease the discharge of Purkinje cells by exciting stellate cell inhibitory interneurons. We describe instances adaptive balance at a behavioral level in which prolonged vestibular or optokinetic stimulation evokes reflexive eye movements that persist when the stimulation that initially evoked them stops. Adaptation to prolonged optokinetic stimulation also can be detected at cellular and subcellular levels. The transcription and expression of a neuropeptide, corticotropin releasing factor (CRF), is influenced by optokinetically-evoked olivary discharge and may contribute to optokinetic adaptation. The transcription and expression of microRNAs in floccular Purkinje cells evoked by long-term optokinetic stimulation may provide one of the subcellular mechanisms by which the membrane insertion of the GABAA receptors is regulated. The neurosteroids, estradiol (E2) and dihydrotestosterone (DHT), influence adaptation of vestibular nuclear neurons to electrically-induced potentiation and depression. In each section of this review, we discuss how adaptive changes in the vestibular and optokinetic subsystems of lobule X, inferior olivary nuclei and vestibular nuclei may contribute to the control of balance.

scholarly journals Modulated discharge of Purkinje and stellate cells persists after unilateral loss of vestibular primary afferent mossy fibers in mice

2013 ◽  
Vol 110 (10) ◽  
pp. 2257-2274 ◽  
Author(s):  
N. H. Barmack ◽  
V. Yakhnitsa
Keyword(s):  
Purkinje Cells ◽  
Stellate Cell ◽  
Mossy Fibers ◽  
Stellate Cells ◽  
Climbing Fibers ◽  
Afferent Pathways ◽  
Parallel Fibers ◽  
Primary Afferent ◽  
Low Frequencies ◽  
Cell Discharge

Cerebellar Purkinje cells are excited by two afferent pathways: climbing and mossy fibers. Climbing fibers evoke large “complex spikes” (CSs) that discharge at low frequencies. Mossy fibers synapse on granule cells whose parallel fibers excite Purkinje cells and may contribute to the genesis of “simple spikes” (SSs). Both afferent systems convey vestibular information to folia 9c–10. After making a unilateral labyrinthectomy (UL) in mice, we tested how the discharge of CSs and SSs was changed by the loss of primary vestibular afferent mossy fibers during sinusoidal roll tilt. We recorded from cells identified by juxtacellular neurobiotin labeling. The UL preferentially reduced vestibular modulation of CSs and SSs in folia 8–10 contralateral to the UL. The effects of a UL on Purkinje cell discharge were similar in folia 9c–10, to which vestibular primary afferents project, and in folia 8–9a, to which they do not project, suggesting that vestibular primary afferent mossy fibers were not responsible for the UL-induced alteration of SS discharge. UL also induced reduced vestibular modulation of stellate cell discharge contralateral to the UL. We attribute the decreased modulation to reduced vestibular modulation of climbing fibers. In summary, climbing fibers modulate CSs directly and SSs indirectly through activation of stellate cells. Whereas vestibular primary afferent mossy fibers cannot account for the modulated discharge of SSs or stellate cells, the nonspecific excitation of Purkinje cells by parallel fibers may set an operating point about which the discharges of SSs are sculpted by climbing fibers.

Vestibular and visual climbing fiber signals evoked in the uvula-nodulus of the rabbit cerebellum by natural stimulation

1995 ◽  
Vol 74 (6) ◽  
pp. 2573-2589 ◽  
Author(s):  
N. H. Barmack ◽  
H. Shojaku
Keyword(s):  
Purkinje Cells ◽  
Semicircular Canal ◽  
Mossy Fiber ◽  
Semicircular Canals ◽  
Longitudinal Axis ◽  
Climbing Fiber ◽  
Optokinetic Stimulation ◽  
Simple Spike ◽  
Postural Responses ◽  
Stimulation Of

1. The cerebellar uvula-nodulus receives vestibular projections from primary and secondary vestibular afferents as well as vestibularly related climbing fibers. It also receives visually related information from climbing fiber pathways. In this experiment we investigated how this information is mapped onto the uvula-nodulus. We studied the specificity, dynamics, and topographic distribution of climbing fiber responses (CFRs), simple spike responses, and mossy fiber terminal responses evoked by vestibular and optokinetic stimulation in rabbits anesthetized with alpha-chloralose. 2. Vestibularly evoked CFRs were found in the ventral uvula and nodulus. These responses were evoked during static roll tilt of the rabbit about a longitudinal axis and by sinusoidal oscillation about the longitudinal axis. Purely static responses were attributed to stimulation of the utricular otolith by the linear acceleration of gravity. CFRs that lacked a static component were attributed to activation of the semicircular canals. 3. Using a "null technique" we showed that the canal-sensitive CFRs were caused by stimulation of the anterior or posterior semicircular canals. Of the CFRs classified as canal related, 96% could be attributed to stimulation of the vertical semicircular canals. 4. Increases in CFRs were correlated with decreases in simple spike responses in half the Purkinje cells from which we recorded. These climbing-fiber-induced pauses in simple spikes occurred during spontaneous climbing fiber discharge as well as during climbing fiber discharge evoked by vestibular stimulation. The duration of this pause was inversely proportional to the spontaneous level of simple spikes before the occurrence of a CFR. In the other half of the recorded population of Purkinje cells, vestibularly driven CFRs did not alter the simple spike responses. 5. Vestibularly and visually mediated CFRs were topographically represented on the surface of the uvula-nodulus. CFRs driven by ipsilateral otolithic inputs were distributed over the entire mediolateral surface of the uvula-nodulus. CFRs driven by the ipsilateral posterior semicircular canal were distributed in a sagittal strip approximately 1.5 mm wide, extending laterally from the midline of the nodulus. CFRs driven exclusively by horizontal, posterior-->anterior optokinetic stimulation of the ipsilateral eye were distributed in a sagittal strip approximately 0.5 mm wide located 0.5-1.0 mm from the midline and restricted to the ventral nodulus. CFRs driven by the ipsilateral anterior semicircular canal were found in a sagittal strip approximately 1.0 mm wide extending 1.0-2.0 mm from the midline. 6. The sagittal, topographically arrayed climbing fiber strips effectively map a mediolateral gradient of possible postural responses based on vestibular and optokinetic information.

Input of Anterior and Posterior Semicircular Canal Interneurons Encoding Head-Velocity to the Dorsal Y Group of the Vestibular Nuclei

2000 ◽  
Vol 83 (5) ◽  
pp. 2891-2904 ◽  
Author(s):  
Pablo Blazquez ◽  
Agis Partsalis ◽  
Nicolaas M. Gerrits ◽  
Stephen M. Highstein
Keyword(s):  
Electric Pulse ◽  
Semicircular Canals ◽  
Mossy Fibers ◽  
Vestibular Nuclei ◽  
Vestibuloocular Reflex ◽  
Interspike Intervals ◽  
Posterior Semicircular Canal ◽  
Viiith Nerve ◽  
Ventral Paraflocculus ◽  
Pulse Stimulation

Neurons in the Y group of the vestibular nuclei are activated disynaptically from the ipsilateral VIIIth nerve and polysynaptically from the contralateral nerve. The ipsilateral anterior and posterior semicircular canals project to the Y group via interneurons in the vestibular nuclei. Candidate interneurons located in the rostrolateral corner of the superior (SVN) and in the caudal medial (MVN) vestibular nuclei were retrogradely labeled by the iontophoretic injection of biocytin into the Y group. The physiology of these interneurons named Y-group projecting neurons (YPNs) was studied in the SVN. SVN-YPNs were activated antidromically by electric pulse stimulation in the Y group. The properties of SVN-YPNs are distinct from those of SVN flocculus projecting neurons (FPNs). Namely, YPNs have a lower resting rate than FPNs, have more irregular interspike intervals, show a different phase and gain during the vestibuloocular reflex, and are located differentially within the SVN. After the injection of biocytin into the Y group, the locations of Purkinje cells that project to the Y group were confined to the vertical zones of the flocculus and ventral paraflocculus. However, mossy fibers originating in the Y group terminate in both the vertical and horizontal zones of the flocculus and ventral paraflocculus as well as in the ipsilateral nodulus.

scholarly journals Axons from the Trigeminal Ganglia are the Earliest Afferent Projections to the Mouse Cerebellum

2017 ◽  
Author(s):  
Hassan Marzban ◽  
Maryam Rahimi-Balaei ◽  
Richard Hawkes
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Mossy Fibers ◽  
Cell Plate ◽  
Trigeminal System ◽  
Trigeminal Ganglia ◽  
Afferent Pathways ◽  
Afferent Projections

ABSTRACTThe first stage standard model for the development of afferent pathways to the cerebellum is that ingrowing axons target the embryonic Purkinje cells (E13-E16 in mice). Perinatally and early postnatal (E18-P15) the climbing fibers translocate to the Purkinje cell dendrites, and as the granular layer develops the mossy fibers translocate from the Purkinje cell somata and synapse with granule cell dendrites. In this report we describe a novel earlier stage in the development. Immunostaining for a neurofilament-associated antigen (NAA) reveals the early axon distributions with remarkable clarity. Axons from the trigeminal system enter the cerebellar primordium as early as embryo age (E)9. By using a combination of axon tract tracing, analysis of neurogenin1 null mice – which do not develop trigeminal ganglia – and mouse embryos maintained in vitro – we show that the first axons to innervate the cerebellar primordium are direct projections from the trigeminal ganglia. The data show that the early trigeminal projections are in situ before the Purkinje cells are born, and double immunostaining for NAA and markers of the different domains in the cerebellar primordium reveal that they first target the cerebellar nuclear neurons of the nuclear transitory zone (E9-E10), and only later (E10-E11) extend collateral branches to the Purkinje cell plate.

Complex Spike Activity of Purkinje Cells in the Ventral Uvula and Nodulus of Pigeons in Response to Translational Optic Flow

1999 ◽  
Vol 81 (1) ◽  
pp. 256-266 ◽  
Author(s):  
Douglas R. W. Wylie ◽  
Barrie J. Frost
Keyword(s):  
Purkinje Cells ◽  
Optic Flow ◽  
Spike Activity ◽  
Semicircular Canals ◽  
Vertical Axis ◽  
Postural Control System ◽  
Complex Spike ◽  
Forward Translation ◽  
Self Motion ◽  
Direction Preference

Wylie, Douglas R. W. and Barrie J. Frost. Complex spike activity of Purkinje cells in the ventral uvula and nodulus of pigeons in response to translational optic flow. J. Neurophysiol. 81: 256–266, 1999. The complex spike (CS) activity of Purkinje cells in the ventral uvula and nodulus of the vestibulocerebellum was recorded from anesthetized pigeons in response to translational optic flow. Translational optic flow was produced using a “translator” projector: a mechanical device that projected a translational optic flowfield onto the walls, ceiling, and floor of the room and encompassed the entire binocular visual field. CS activity was broadly tuned but maximally modulated in response to translational optic flow along a “best” axis. Each neuron was assigned a vector representing the direction in which the animal would need to translate to produce the optic flowfield that resulted in maximal excitation. The vector is described with reference to a standard right-handed coordinate system, where the vectors, + x, + y, and + z represent, rightward, upward, and forward translation of the animal, respectively. Neurons could be grouped into four response types based on the vector of maximal excitation. + y neurons were modulated maximally in response to a translational optic flowfield that results from self-motion upward along the vertical ( y) axis. − y neurons also responded best to translational optic flow along the vertical axis but showed the opposite direction preference. The two remaining groups responded best to translational optic flow along horizontal axes: − x + z neurons and − x− z neurons. In summary, our results suggest that the olivocerebellar system dedicated to the analysis of translational optic flow is organized according to a reference frame consisting of three approximately orthogonal axes: the vertical axis, and two horizontal axes oriented 45° to either side the midline. Previous research has shown that the rotational optic flow system, the eye muscles, the vestibular semicircular canals and the postural control system all share a similar spatial frame of reference.

scholarly journals Sensorimotor impairment from a new analog of spaceflight-altered neurovestibular cues

2020 ◽  
Vol 123 (1) ◽  
pp. 209-223
Author(s):  
Jordan B. Dixon ◽  
Torin K. Clark
Keyword(s):  
Head Tilt ◽  
Semicircular Canals ◽  
Control Groups ◽  
Head Restraint ◽  
The Subject ◽  
Sensorimotor Impairment ◽  
Self Motion ◽  
Future Work ◽  
Extended Exposure ◽  
Sensorimotor Performance

Exposure to microgravity during spaceflight causes central reinterpretations of orientation sensory cues in astronauts, leading to sensorimotor impairment upon return to Earth. Currently there is no ground-based analog for the neurovestibular system relevant to spaceflight. We propose such an analog, which we term the “wheelchair head-immobilization paradigm” (WHIP). Subjects lie on their side on a bed fixed to a modified electric wheelchair, with their head restrained by a custom facemask. WHIP prevents any head tilt relative to gravity, which normally produces coupled stimulation to the otoliths and semicircular canals, but does not occur in microgravity. Decoupled stimulation is produced through translation and rotation on the wheelchair by the subject using a joystick. Following 12 h of WHIP exposure, subjects systematically felt illusory sensations of self-motion when making head tilts and had significant decrements in balance and locomotion function using tasks similar to those assessed in astronauts postspaceflight. These effects were not observed in our control groups without head restraint, suggesting the altered neurovestibular stimulation patterns experienced in WHIP lead to relevant central reinterpretations. We conclude by discussing the findings in light of postspaceflight sensorimotor impairment, WHIP’s uses beyond a spaceflight analog, limitations, and future work. NEW & NOTEWORTHY We propose, implement, and demonstrate the feasibility of a new analog for spaceflight-altered neurovestibular stimulation. Following extended exposure to the analog, we found subjects reported illusory self-motion perception. Furthermore, they demonstrated decrements in balance and locomotion, using tasks similar to those used to assess astronaut sensorimotor performance postspaceflight.

Impacts of Rotation Axis and Frequency on Vestibular Perceptual Thresholds

2022 ◽  
pp. 1-29
Author(s):  
Andrew R. Wagner ◽  
Megan J. Kobel ◽  
Daniel M. Merfeld
Keyword(s):  
Multisensory Integration ◽  
Rotation Axis ◽  
Semicircular Canals ◽  
Rotation Velocity ◽  
Pass Filter ◽  
Motion Cues ◽  
Left Posterior ◽  
Rotation Plane ◽  
Self Motion ◽  
Lower Frequencies

Abstract In an effort to characterize the factors influencing the perception of self-motion rotational cues, vestibular self-motion perceptual thresholds were measured in 14 subjects for rotations in the roll and pitch planes, as well as in the planes aligned with the anatomic orientation of the vertical semicircular canals (i.e., left anterior, right posterior; LARP, and right anterior, left posterior; RALP). To determine the multisensory influence of concurrent otolith cues, within each plane of motion, thresholds were measured at four discrete frequencies for rotations about earth-horizontal (i.e., tilts; EH) and earth-vertical axes (i.e., head positioned in the plane of the rotation; EV). We found that the perception of rotations, stimulating primarily the vertical canals, was consistent with the behavior of a high-pass filter for all planes of motion, with velocity thresholds increasing at lower frequencies of rotation. In contrast, tilt (i.e, EH rotation) velocity thresholds, stimulating both the canals and otoliths (i.e., multisensory integration), decreased at lower frequencies and were significantly lower than earth-vertical rotation thresholds at each frequency below 2 Hz. These data suggest that multisensory integration of otolithic gravity cues with semicircular canal rotation cues enhances perceptual precision for tilt motions at frequencies below 2 Hz. We also showed that rotation thresholds, at least partially, were dependent on the orientation of the rotation plane relative to the anatomical alignment of the vertical canals. Collectively these data provide the first comprehensive report of how frequency and axis of rotation influence perception of rotational self-motion cues stimulating the vertical canals.

Probing the human vestibular system with galvanic stimulation

2004 ◽  
Vol 96 (6) ◽  
pp. 2301-2316 ◽  
Author(s):  
Richard C. Fitzpatrick ◽  
Brian L. Day
Keyword(s):  
Balance Control ◽  
Semicircular Canals ◽  
Vestibular Nuclei ◽  
Vestibular Stimulation ◽  
Otolith Organs ◽  
Sources Of Information ◽  
Electrophysiological Studies ◽  
Human Balance ◽  
Cortical Inputs ◽  
Vestibular Organs

Galvanic vestibular stimulation (GVS) is a simple, safe, and specific way to elicit vestibular reflexes. Yet, despite a long history, it has only recently found popularity as a research tool and is rarely used clinically. The obstacle to advancing and exploiting GVS is that we cannot interpret the evoked responses with certainty because we do not understand how the stimulus acts as an input to the system. This paper examines the electrophysiology and anatomy of the vestibular organs and the effects of GVS on human balance control and develops a model that explains the observed balance responses. These responses are large and highly organized over all body segments and adapt to postural and balance requirements. To achieve this, neurons in the vestibular nuclei receive convergent signals from all vestibular receptors and somatosensory and cortical inputs. GVS sway responses are affected by other sources of information about balance but can appear as the sum of otolithic and semicircular canal responses. Electrophysiological studies showing similar activation of primary afferents from the otolith organs and canals and their convergence in the vestibular nuclei support this. On the basis of the morphology of the cristae and the alignment of the semicircular canals in the skull, rotational vectors calculated for every mode of GVS agree with the observed sway. However, vector summation of signals from all utricular afferents does not explain the observed sway. Thus we propose the hypothesis that the otolithic component of the balance response originates from only the pars medialis of the utricular macula.

scholarly journals Cerebellar implementation of movement sequences through feedback

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Andrei Khilkevich ◽  
Juan Zambrano ◽  
Molly-Marie Richards ◽  
Michael Dean Mauk
Keyword(s):  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
General Framework ◽  
Eyelid Conditioning ◽  
Mossy Fibers ◽  
Learning Processes ◽  
Single Component ◽  
Associate Learning ◽  
Stimulation Of

Most movements are not unitary, but are comprised of sequences. Although patients with cerebellar pathology display severe deficits in the execution and learning of sequences (Doyon et al., 1997; Shin and Ivry, 2003), most of our understanding of cerebellar mechanisms has come from analyses of single component movements. Eyelid conditioning is a cerebellar-mediated behavior that provides the ability to control and restrict inputs to the cerebellum through stimulation of mossy fibers. We utilized this advantage to test directly how the cerebellum can learn a sequence of inter-connected movement components in rabbits. We show that the feedback signals from one component are sufficient to serve as a cue for the next component in the sequence. In vivo recordings from Purkinje cells demonstrated that all components of the sequence were encoded similarly by cerebellar cortex. These results provide a simple yet general framework for how the cerebellum can use simple associate learning processes to chain together a sequence of appropriately timed responses.

scholarly journals Cerebellar and vestibular nuclear synapses in the inferior olive have distinct release kinetics and neurotransmitters

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Josef Turecek ◽  
Wade G Regehr
Keyword(s):  
Purkinje Cells ◽  
Inferior Olive ◽  
Release Kinetics ◽  
Vestibular Nuclei ◽  
Cerebellar Nuclei ◽  
Climbing Fiber ◽  
Inhibitory Input ◽  
Deep Cerebellar Nuclei

The inferior olive (IO) is composed of electrically-coupled neurons that make climbing fiber synapses onto Purkinje cells. Neurons in different IO subnuclei are inhibited by synapses with wide ranging release kinetics. Inhibition can be exclusively synchronous, asynchronous, or a mixture of both. Whether the same boutons, neurons or sources provide these kinetically distinct types of inhibition was not known. We find that in mice the deep cerebellar nuclei (DCN) and vestibular nuclei (VN) are two major sources of inhibition to the IO that are specialized to provide inhibitory input with distinct kinetics. DCN to IO synapses lack fast synaptotagmin isoforms, release neurotransmitter asynchronously, and are exclusively GABAergic. VN to IO synapses contain fast synaptotagmin isoforms, release neurotransmitter synchronously, and are mediated by combined GABAergic and glycinergic transmission. These findings indicate that VN and DCN inhibitory inputs to the IO are suited to control different aspects of IO activity.

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